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Exjade (deferasirox) - Notice of Compliance with Conditions - Qualifying Notice
Date: 2006-11-27
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Therapeutic Products Directorate
Finance Building
101 Tunney's Pasture Driveway
Address Locator# 0202D2
Tunney's Pasture
OTTAWA, Ontario
K1A 0K9
August 17, 2006
9427-N0846-304
[employee's name removed]
Senior Manager, Drug Regulatory Affairs
Novartis Pharmaceuticals Canada Inc.
385 Bouchard Boulevard
DORVAL, Quebec
H9S 1A9
NOTICE OF COMPLIANCE WITH CONDITIONS-QUALIFYING NOTICE
Dear [employee's name removed] :
This Notice of Compliance with Conditions-Qualifying Notice, issued in accordance with the Health Canada NOC/c policy, is to advise you that information submitted in support of the New Drug Submission for EXJADE (deferasirox), Control Number 099621, qualifies to be considered for approval, under the NOC/c policy. In keeping with the provisions outlined in the NOC/c policy, the following additional information is required to complete the assessment:
1.) A letter signed by the Chief Executive Officer, or designated signing authority of Novartis Pharmaceuticals Canada Inc., indicating that you agree to have this submission considered under the NOC/c policy.
2.) A draft Letter of Undertaking signed by the Chief Executive Officer or designated signing authority of Novartis Pharmaceuticals Canada Inc., having a form and content satisfactory to Health Canada , including commitments to supply the following:
Confirmatory studies
- Complete and submit data from the extension studies 105E2, 106E1, 107E1, 108E1 and 109E1 for a total of 4 years after the core trial.
- Pursue assessment of safety and efficacy of Exjade in pediatric patients 2-<6 years of age at study entry through a registry involving approximately 200 children with a 5 year follow-up. Data collection should include at least monthly assessments of renal and hepatic functions, blood pressure measurements and growth and development assessments every 3 months.
- Study the PK of Exjade in patients with hepatic impairment [not included in the Letter of Undertaking] and at doses of 20 [not included in the Letter of Undertaking] mg/kg per day.
- In view of the fact that 20 mg/kg could maintain body iron burden, conduct clinical studies in adult and pediatric patients with congenital or acquired anemias and chronic iron overload and a LIC < 7 mg Fe/g dw liver treated with Exjade at doses of 20 or 30 mg/kg per day.
- Complete study of long-term follow-up in 150 patients with myelodysplastic syndromes receiving Exjade, including patients with baseline serum creatinine values up to 2 x ULN, to better define cardiac, hepatic, endocrine and renal functions, and haematological and clinical benefit of Exjade for a duration of follow-up on Exjade of at least 3 years.
- Evaluate cardiac iron and cardiac function as well as clinical outcomes to explore the relationship amongst iron body burden as measured by LIC, cardiac iron, serum ferritin, transfusion rates and clinical endpoints in patients treated with Exjade.
Post marketing safety monitoring studies
- Conduct a renal mechanistic study [information removed].
- Conduct a hepatic study [information removed].
- Conduct an ophthalmologic study in at least 60 patients receiving Exjade with 2 years follow-up. Examinations should include distance visual acuity, lens photography and wide angle fundus photography of retina and optic nerve and done at baseline, prior to initiating Exjade, and at six month intervals.
- [commitment iv removed, as it was not included in the Letter of Undertaking].
- Report of all serious ADRs that occurred in Canada and all serious unexpected ADRs that occurred outside of Canada should be forwarded within 15 days to the Marketed Health Products Directorate and the appropriate review bureau in Therapeutic Products Directorate in accordance with current regulations and guidelines.
- Periodic Safety Update Reports (PSUR-Cs), to be submitted semi-annually, until the conditions have been fulfilled and removed from the NOC/c by Health Canada. PSURs should be prepared in accordance with ICH Guidelines.
3.) A draft of the "Dear Health Care Professional Letter" detailing the conditional approval of EXJADE.
4.) A draft of the "Fact Sheet", outlining in lay language the risks and benefits and side effects of the new indication for EXJADE.
5.) A draft of the Product Monograph which is consistent with the requirements outlined in section 5.2.1 of the Notice of Compliance with Conditions Guidance. Please note that, if applicable, a boxed text must appear on the cover page, at the beginning of each major section of the Product Monograph (Parts I, II and III) and the first page and the start of the Consumer Information section.
I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada 's guidance and policy on the Management of Drug Submissions and Notice of Compliance with Conditions, respectively. Sponsors are instructed to submit a complete response (refer to "Guidance for Industry; Notice of Compliance with Conditions") to the outstanding information within 30 calendar days of the date of this letter.
In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to Chief, Submission and Information Policy Division, Bureau of Operational Services, Therapeutic Products Directorate, Finance Building, Tunney's Pasture, Address Locator 0201A1, Ottawa, Ontario, K1A 0K9.
Yours sincerely,
Original signed by
Barbara Rotter, Ph.D.
Director
Bureau of Metabolism, Oncology and Reproductive Sciences
Tel: (613) 941-1154
Fax: (613) 941-1365
